Electronic Structural Trends in Divalent Carbon Compounds

This work aims to analyze and compare the intrinsic electronic densities in a series of neutral and anionic divalent carbon-donor derivatives. The σ-lone pair at the divalent carbon is the HOMO of these species. Structural factors have been identified that influence its energy, which is a measure of the σ-basicity. The π-electronic structure has been described as a function of the π-population. Our results show that no straightforward structural criteria correlate with the π-electronic distribution. However, the π-population, as well as the π-acidity and π-basicity, are related to the π-MOs. In all cases, these π-MOs can be qualitatively obtained on the basis of those of the protonated analogues by simply increasing the energy of the p_π orbital at the divalent carbon atom compared to normal sp² carbon. Such an analysis allows a rationalization of the trends observed for the π-electronic structure of these ligands. Notably, this explains the values of the π-population at the divalent carbon center, which shows an increasing and continuous range from classical NHCs to mesoionic “carbenes”

Benchmarking DFT and TD-DFT Functionals for the Ground and Excited States of Hydrogen-Rich Peptide Radicals

We assess the pros and cons of a large panel of DFT exchange-correlation functionals for the prediction of the electronic structure of hydrogen-rich peptide radicals formed after electron attachment on a protonated peptide. Indeed, despite its importance in the understanding of the chemical changes associated with the reduction step, the question of the attachment site of an electron and, more generally, of the reduced species formed in the gas phase through electron-induced dissociation (ExD) processes in mass spectrometry is still a matter of debate. For hydrogen-rich peptide radicals in which several positive groups and low-lying π* orbitals can capture the incoming electron in ExD, inclusion of full Hartree–Fock exchange at long-range interelectronic distance is a prerequisite for an accurate description of the electronic states, thereby excluding several popular exchange-correlation functionals, e.g., B3LYP, M06-2X, or CAM-B3LYP. However, we show that this condition is not sufficient by comparing the results obtained with asymptotically correct range-separated hybrids (M11, LC-BLYP, LC-BPW91, ωB97, ωB97X, and ωB97X-D) and with reference CASSCF-MRCI and EOM-CCSD calculations. The attenuation parameter ω significantly tunes the spin density distribution and the excited states vertical energies. The investigated model structures, ranging from methylammonium to hexapeptide, allow us to obtain a description of the nature and energy of the electronic states, depending on (i) the presence of hydrogen bond(s) around the cationic site(s), (ii) the presence of π* molecular orbitals (MOs), and (iii) the selected DFT approach. It turns out that, in the present framework, LC-BLYP and ωB97 yields the most accurate results

Revised Theoretical Model on Enantiocontrol in Phosphoric Acid Catalyzed <i>H</i>‑Transfer Hydrogenation of Quinoline

The enantioselective H-transfer hydrogenation of quinoline by Hantzsch ester is a relevant example of Brønsted acid catalyzed cascade reactions, with phosphoric acid being a privileged catalyst. The generally accepted mechanism points out the hydride transfer step as the rate- and stereodetermining step, however computations based on these models do not totally fit with experimental observations. We hereby present a computational study that enlightens the stereochemical outcome and quantitatively reproduces the experimental enantiomeric excesses in a series of H-transfer hydrogenations. Our calculations suggest that the high stereocontrol usually attained with BINOL-derived phosphoric acids results mostly from the steric constraints generated by an aryl substituent of the catalyst, which hinders the access of the Hantzsch ester to the catalytic site and enforces approach through a specific way. It relies on a new model involving the preferential assembly of one of the stereomeric complexes formed by the chiral phosphoric acid and the two reaction partners. The stereodetermining step thus occurs prior to the H-transfer step

Csp²–N Bond Formation via Ligand-Free Pd-Catalyzed Oxidative Coupling Reaction of <i>N</i>‑Tosylhydrazones and Indole Derivatives

In a fresh approach to the synthesis of <i>N</i>-vinylazoles, a ligand-free palladium catalytic system was found to promote the Csp²–N bond-forming reaction utilizing <i>N</i>-tosylhydrazones and N-H azoles. This process shows functional group tolerance; di-, tri-, and tetrasubstituted <i>N</i>-vinylazoles were obtained in high yields. Under the optimized conditions, the reaction proceeds with high stereoselectivity depending on the nature of the coupling partners

Vibrational Signatures of <i>S</i>‑Nitrosoglutathione as Gaseous, Protonated Species

Gas-phase ions of protonated l-glutathione as native species, [GSH + H]⁺, and <i>S</i>-nitroso derivative, [GSNO + H]⁺, have been generated by electrospray ionization and probed via infrared multiple photon dissociation (IRMPD) action spectroscopy. Insight into the conformational landscape is gained from interpretation of the IR spectra aided by high-level theoretical calculations, which enables structural assignment disclosing both the site of protonation and the intramolecular hydrogen-bond network. Calculations yield the low-energy structures of [GSNO + H]⁺. A admixture of the four most stable ones (<b>SN1</b>, <b>AN1</b>, <b>SN2</b>, and <b>AN2</b>) is apt to account for the experimental IRMPD spectra obtained in both the 1000–2000 and the 3100–3700 cm^–1 spectral ranges. The most stable form of [GSNO + H]⁺, <b>SN1</b>, protonated at the amino group, presents a syn conformation at the S–N (partial) double bond and all peptidic carbonyls involved in (strong) CO···H–N hydrogen bonds, so allowing closure of a C5 (β-strand), two C7 (γ-turn), and one C9-membered rings. An appreciable barrier to rotation of 43 kJ mol^–1 about the S–N bond is found to separate <b>SN1</b> from the analogous anti isomer <b>AN1</b>, which lies only 0.70 kJ mol^–1 higher in free energy. Conformers obtained for [GSH + H]⁺ are very similar to the [GSNO + H]⁺ counterparts, indicating that the <i>S</i>-nitrosation motif does not affect significantly the geometry of the peptide. The observed ν­(NO) signatures at 1622 and 1690 cm^–1, merged with other absorptions, are revealed by their sensitivity to ¹⁵NO isotope labeling and by comparison with the IRMPD spectrum of native [GSH + H]⁺, providing a diagnostic probe for the <i>S</i>-nitrosation feature in natural peptides

Csp²–Csp² and Csp²–N Bond Formation in a One-Pot Reaction between <i>N</i>‑Tosylhydrazones and Bromonitrobenzenes: An Unexpected Cyclization to Substituted Indole Derivatives

A novel, sequential, palladium-catalyzed, cross-coupling reaction using <i>N</i>-tosylhydrazone and bromonitrobenzene derivatives followed by reductive cyclization has been developed. This transformation providing an efficient route to unexpected <i>N</i>-arylindole derivatives involves, in a one-pot reaction, the formation of one Csp²–Csp² bond and two Csp²–N bonds together with the cleavage of one Csp²–heteroatom bond. Evaluation of the biological activity led to the identification of compound <b>5a</b>, which displays potent activity at nanomolar concentrations against human colon carcinoma cell line

Ground Electronic State of Peptide Cation Radicals: A Delocalized Unpaired Electron?

Electron capture and electron transfer dissociations are bioanalytical methods for fragmenting cations after reduction by an electron. Previous computational studies based on conventional DFT schemes have concluded that the first step of these processes, the attachment of the electron, leads to extensive delocalization of the spin density in the intermediate radical cation. Here we show that most DFT methods produce unphysical results when studying single electron reduction of a dicationic peptide. This is not the case for post-HF methods and long-range corrected functionals that show satisfying electron affinities, intermolecular interaction energies, and spin density trends. Our results suggest that the charged group with the highest electron affinity on the precursor cation is also the site of spin density in the electronic ground state after electron attachment. These findings have important implications for the interpretation of experimental data from electron-based processes in biomolecules and may guide the development of new functionals

Planar Chiral Phosphoric Acids with Biphenylene-Tethered Paracyclophane Scaffolds: Synthesis, Characterization, and Catalytic Screening

Phosphoric acids with planar chiral paracyclophane scaffolds have been prepared in optically pure form starting from 1,8-dibromobiphenylene, by means of a chiral phosphorodiamidate as the phosphorylating agent. Structural characterization and configurational assignment have been performed by X-ray diffraction studies. The acids promote the organocatalytic enantioselective H-transfer reduction of α-arylquinolines with up to 90% enantiomeric excess